Crystal structures of botulinum neurotoxin DC in complex with its protein receptors synaptotagmin I and II.

Abstract

Botulinum neurotoxins (BoNTs) can cause paralysis at exceptionally low concentrations and include seven serotypes (BoNT/A-G). The chimeric BoNT/DC toxin has a receptor binding domain similar to the same region in BoNT/C. However, BoNT/DC does not share protein receptor with BoNT/C. Instead, it shares synaptotagmin (Syt) I and II as receptors with BoNT/B, despite their low sequence similarity. Here, we present the crystal structures of the binding domain of BoNT/DC in complex with the recognition domains of its protein receptors, Syt-I and Syt-II. The structures reveal that BoNT/DC possesses a Syt binding site, distinct from the established Syt-II binding site in BoNT/B. Structure-based mutagenesis further shows that hydrophobic interactions play a key role in Syt binding. The structures suggest that the BoNT/DC ganglioside binding sites are independent of the protein receptor binding site. Our results reveal the remarkable versatility in the receptor recognition of the BoNTs.

• Authors: Ronnie Per-Arne Berntsson, Lisheng Peng, Linda Marie Svensson, Min Dong, Pål Stenmark
• Journal: Structure (London, England : 1993) (Structure) Vol. 21 Issue 9 Pg. 1602-11 (Sep 03 2013) ISSN: 1878-4186 [Electronic] United States
• PMID: 23932591 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• SYT1 protein, human
• Synaptotagmin I
• Synaptotagmin II
• Syt2 protein, rat
• botulinum toxin type D
• Botulinum Toxins
• botulinum toxin type C

Topics

• Amino Acid Sequence
• Animals
• Binding Sites
• Botulinum Toxins (chemistry)
• Clostridium botulinum
• Crystallography, X-Ray
• Humans
• Hydrogen Bonding
• Models, Molecular
• Molecular Sequence Data
• Protein Interaction Domains and Motifs
• Protein Structure, Quaternary
• Protein Structure, Secondary
• Rats
• Structural Homology, Protein
• Synaptotagmin I (chemistry)
• Synaptotagmin II (chemistry)